NM_130810.4:c.454C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_130810.4(DNAAF4):c.454C>T(p.Arg152Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000252 in 1,533,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R152Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

DNAAF4
NM_130810.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.70

Publications

4 publications found

Variant links:

Genes affected

DNAAF4 (HGNC:21493): (dynein axonemal assembly factor 4) This gene encodes a tetratricopeptide repeat domain-containing protein. The encoded protein interacts with estrogen receptors and the heat shock proteins, Hsp70 and Hsp90. An homologous protein in rat has been shown to function in neuronal migration in the developing neocortex. A chromosomal translocation involving this gene is associated with a susceptibility to developmental dyslexia. Mutations in this gene are associated with deficits in reading and spelling. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream cell cycle progression 1 (CCPG1) gene. [provided by RefSeq, Mar 2011]

DNAAF4 links:

DNAAF4-CCPG1 (HGNC:43019): (DNAAF4-CCPG1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring dyslexia susceptibility 1 candidate 1 (DYX1C1) and cell cycle progression 1 (CCPG1) genes on chromosome 15. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

DNAAF4-CCPG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.31798714).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130810.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAAF4	NM_130810.4	MANE Select	c.454C>T	p.Arg152Trp	missense	Exon 5 of 10	NP_570722.2	Q8WXU2-1
DNAAF4	NM_001033560.2		c.454C>T	p.Arg152Trp	missense	Exon 5 of 9	NP_001028732.1	Q8WXU2-2
DNAAF4	NM_001033559.3		c.454C>T	p.Arg152Trp	missense	Exon 5 of 9	NP_001028731.1	Q8WXU2-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAAF4	ENST00000321149.7	TSL:1 MANE Select	c.454C>T	p.Arg152Trp	missense	Exon 5 of 10	ENSP00000323275.3	Q8WXU2-1
DNAAF4	ENST00000448430.6	TSL:1	c.454C>T	p.Arg152Trp	missense	Exon 4 of 8	ENSP00000403412.2	Q8WXU2-2
DNAAF4	ENST00000457155.6	TSL:1	c.454C>T	p.Arg152Trp	missense	Exon 4 of 8	ENSP00000402640.2	Q8WXU2-3

Frequencies

GnomAD3 genomes

AF:

0.000226

AC:

AN:

150260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000333

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.000210

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000399

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000169

AC:

AN:

154206

AF XY:

0.000169

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000157

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000941

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000312

Gnomad OTH exome

AF:

0.000236

GnomAD4 exome

AF:

0.000255

AC:

353

AN:

1383450

Hom.:

Cov.:

AF XY:

0.000259

AC XY:

177

AN XY:

683590

show subpopulations

African (AFR)

AF:

0.0000669

AC:

AN:

29906

American (AMR)

AF:

0.000200

AC:

AN:

30018

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24608

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35750

South Asian (SAS)

AF:

0.0000405

AC:

AN:

74108

European-Finnish (FIN)

AF:

0.0000201

AC:

AN:

49682

Middle Eastern (MID)

AF:

0.000357

AC:

AN:

5600

European-Non Finnish (NFE)

AF:

0.000299

AC:

322

AN:

1076640

Other (OTH)

AF:

0.000280

AC:

AN:

57138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000226

AC:

AN:

150376

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

AN XY:

73314

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40896

American (AMR)

AF:

0.000332

AC:

AN:

15052

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.000195

AC:

AN:

5118

South Asian (SAS)

AF:

0.000210

AC:

AN:

4766

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10088

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000399

AC:

AN:

67696

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000317

Hom.:

Bravo

AF:

0.000208

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.000137

AC:

Asia WGS

AF:

0.000580

AC:

AN:

3464

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Dyslexia, susceptibility to, 1;C3809641:Primary ciliary dyskinesia 25 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.024

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.98

PhyloP100

1.7

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.15

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.73

MVP

0.62

MPC

0.33

ClinPred

0.27

GERP RS

3.6

Varity_R

0.23

gMVP

0.52

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over